Reduction in MCP-1 production in preadipocytes is mediated by PPARγ activation and JNK/SIRT1 signaling

Obesity-induced monocyte chemoattractant protein 1 (MCP-1) production leads to the infiltration of monocytes/macrophages into white adipose tissue (WAT), which contributes to systemic insulin resistance. Peroxisome proliferator-activated receptor gamma (PPARγ) agonists are known to reduce MCP-1 prod...

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Vydané v:	Biochimica et biophysica acta. General subjects Ročník 1869; číslo 2; s. 130737
Hlavní autori:	Sawamoto, Atsushi, Itagaki, Ibuki, Okuyama, Satoshi, Nakajima, Mitsunari
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Netherlands Elsevier B.V 01.02.2025
Predmet:	3T3-L1 Cells Adipocytes - drug effects Adipocytes - metabolism Animals C-Jun N-terminal kinase (JNK) Chemokine CCL2 - biosynthesis Chemokine CCL2 - metabolism Insulin resistance JNK Mitogen-Activated Protein Kinases - metabolism Lipopolysaccharides - pharmacology MAP Kinase Signaling System - drug effects Mice Mice, Inbred C57BL Monocyte chemoattractant protein 1 (MCP-1) Peroxisome proliferator-activated receptor gamma (PPARγ) PPAR gamma - agonists PPAR gamma - genetics PPAR gamma - metabolism Preadipocytes Rosiglitazone Signal Transduction - drug effects Silent information regulator 2 homolog 1 (SIRT1) Sirtuin 1 - metabolism Thiazolidinediones - pharmacology PBS MCP-1 SVF JNK RSG Preadipocytes Monocyte chemoattractant protein 1 (MCP-1) WAT C-Jun N-terminal kinase (JNK) LPS BSA DMEM LDH FBS Silent information regulator 2 homolog 1 (SIRT1) Insulin resistance Peroxisome proliferator-activated receptor gamma (PPARγ) SEM ELISA
ISSN:	0304-4165, 1872-8006, 1872-8006
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Shrnutí:	Obesity-induced monocyte chemoattractant protein 1 (MCP-1) production leads to the infiltration of monocytes/macrophages into white adipose tissue (WAT), which contributes to systemic insulin resistance. Peroxisome proliferator-activated receptor gamma (PPARγ) agonists are known to reduce MCP-1 production in both humans and mice; however, the underlying mechanism in WAT remains unclear. Here, we propose a novel mechanism for the reduction in MCP-1 production in preadipocytes. The PPARγ agonist rosiglitazone (RSG) reduced MCP-1 production and secretion in response to lipopolysaccharide (LPS) in 3T3-L1 preadipocytes and mouse stromal vascular fraction–derived primary preadipocytes. Both RSG and SP600125 (a c-Jun N-terminal kinase (JNK) inhibitor) inhibited LPS-induced degradation of silent information regulator 2 homolog 1 (SIRT1), a negative regulator of MCP-1 production in 3T3-L1 preadipocytes. Furthermore, RSG inhibited LPS-induced activation of nuclear factor-κB. These effects of RSG were abolished in 3T3-L1 preadipocytes transfected with Pparg siRNA. These findings highlight a novel mechanism by which PPARγ activation inhibits JNK/SIRT1 signaling in preadipocytes and contributes to the reduction in MCP-1 production, suggesting that preadipocytes could be a potential therapeutic target for the treatment of insulin resistance. •PPARγ is required for the reduction in LPS-induced MCP-1 production in 3T3-L1 and SVF-derived preadipocytes.•Rosiglitazone, a PPARγ agonist, inhibits the activation of JNK and degradation of SIRT1 in 3T3-L1 and SVF-derived preadipocytes.•Inhibition of the JNK/SIRT1 signaling pathway in preadipocytes may be a key mechanism underlying the reduction in MCP-1 production.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0304-4165 1872-8006 1872-8006
DOI:	10.1016/j.bbagen.2024.130737